These studies focus on two topics: ovarian cancer and the Wnt pathway in human cancers. Ovarian cancer is the fifth most common cancer and the fourth leading cause of cancer death among women in the United States. Because of a lack of powerful screening and diagnostic tests, early detection has been difficult. Moreover, the molecular mechanisms involved in the initiation and progression of ovarian cancer remain largely unknown. We are using SAGE and other state-of-the-art molecular techniques to identify tumor markers and gain a greater understanding of the molecular pathways involved in ovarian tumorigenesis. In addition, we are interested in a region on the chromosome 6, which appears to be lost early in ovarian cancer, suggesting the presence of a tumor suppressor gene involved in the first stages of tumor development. We have now found a homozygous deletion spanning approximately 85 kb at 6q26 in an ovarian cancer cell line. This homozygous deletion may help us to identify the 6q tumor suppressor gene. The Wnt pathway, which was originally defined as a crucial pathway for body patterning during fruit fly development, has recently been implicated in human cancer. APC, a gene mutated in 80% of all colon cancers, is involved in the downregulation of the Wnt pathway. Moreover, colon tumors containing wild-type APC, frequently contain activating mutations in other members of the pathway emphasizing its importance for colon cancer progression. We are developing inducible systems that may be useful in the identification of downstream transcriptional targets as well as upstream regulatory components of the pathway .